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Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a devastating effect on the world's population resulting in more than 2 8 million deaths worldwide and emerging as the most significant global health crisis since the influenza pandemic of 1918 Since being declared a global pandemic by the World Health Organization (WHO) on March 11, 2020, the virus continues to cause devastation, with many countries enduring a second or a third wave of outbreaks of this viral illness Adaptive mutations in the viral genome can alter the virus's pathogenic potential Even a single amino acid exchange can drastically affect a virus's ability to evade the immune system and complicate the vaccine development progress against the virus [1] SARS-CoV-2, like other RNA viruses, is prone to genetic evolution while adapting to their new human hosts with the development of mutations over time, resulting in the emergence of multiple variants that may have different characteristics compared to its ancestral strains Periodic genomic sequencing of viral samples helps detect any new genetic variants of SARS-CoV-2 circulating in communities, especially in a global pandemic setting The genetic evolution of SARS-CoV-2 was minimal during the early phase of the pandemic with the emergence of a globally dominant variant called D614G, which was associated with higher transmissibility but without increased disease severity of its ancestral strain [2] Another variant was identified in humans, attributed to transmission from infected farmed mink in Denmark, which was not associated with increased transmissibility [3] Since then, multiple variants of SARS-CoV-2 have been described, of which a few are considered variants of concern (VOCs), given their impact on public health VOCs are associated with enhanced transmissibility or virulence, reduction in neutralization by antibodies obtained through natural infection or vaccination, the ability to evade detection, or a decrease in therapeutics or vaccination effectiveness The first VOC, the B 1 1 7 lineage (or VOC 202012), was described in the United Kingdom (UK) in late December 2020, followed shortly by the detection of the B 1 351 lineage (or 501Y V2) in South Africa In early January 2021, a new VOC, B 1 1 248/B1 1 28/P1 (or 501Y V3), was reported in Brazil, and more recently, the B 1 427/B 1 429 lineage was identified in California The B 1 427/B 1 429 lineage is classified as VOC by the US Centers for Disease Control and Prevention (CDC) but is considered a variant of interest by the WHO All three reported VOCs (B 1 1 7 variant, B 1 351 variant, and P 1 variant) harbor mutations in the receptor-binding domain (RBD) and the N-terminal domain (NTD), of which the N501Y mutation located on the RBD is common to all variants RBD plays a vital role in facilitating viral entry into the host cell by binding to the host cell angiotensin-converting enzyme-2 (ACE-2) receptors Along with NBD, it is the dominant neutralization target and facilitates antibody production in response to antisera or vaccines [4] Two recent preprint studies (not peer-reviewed) reported that a single mutation of N501Y alone increases the affinity between RBD and ACE2 approximately ten times more than the ancestral strain (N501-RBD) Interestingly the binding affinity of B 1 351 variant and P 1 variant with mutations N417/K848/Y501-RBD and ACE2 was much lower than that of N501Y-RBD and ACE2 [5][6] Despite the extraordinary speed of vaccine development against COVID-19 and continued mass vaccination efforts across the world, the emergence of these new variant strains of SARS-CoV-2 threatens to overturn the significant progress made so far in halting the spread of SARS-CoV-2 This review article aims to comprehensively describe these new variants of concern, the latest therapeutics available in managing COVID-19 in adults, and the efficacy of different available vaccines against this virus and its new variants SARS-CoV-2 Variant